Coronary Endothelial Function in Humans

Project: Research project

Project Details


DESCRIPTION (provided by applicant):
Coronary artery disease remains the leading cause of morbidity and mortality
in the Western society and is expected to be the leading cause of morbidity
and mortality worldwide. It becomes apparent that in order to attenuate the
disease process, clinical investigation into the mechanism, diagnosis and
treatment of early coronary atherosclerosis is crucial. Early coronary
atherosclerosis is associated with altered coronary endothelial function
prior to the development of significant atherosclerotic disease. This
disease stage is characterized by coronary vasoconstriction and reduction
or attenuated coronary vasorelaxant response to the endothelial-dependent
vasodilators such as acetylcholine and is associated with myocardial perfusion
defects consistent with myocardial ischemia and an increase in cardiac events.
Thus, the current K-24 application seeks to support the principal investigator
to devote time to patient-oriented research and to act as a mentor for
beginning clinical investigators in the area of early coronary atherosclerosis
and endothelial function in humans. The exceptional patient-oriented research
environment at the Mayo Clinic further optimized by the auspices of the Mayo
Clinic Cardiac Catheterization Laboratory constitutes a unique resource
to address these questions thereby providing a rich experience in patient
oriented research to junior investigators. Thus, building on methods
implemented during the P.I.?s R01 grant, in conjunction with novel and
prospective approaches, the objective of this K24 application is to develop
a program to mentor future investigators in patient-oriented research. The broad scientific aims of this application are: 1) to determine the role
of endothelial humoral regulation of the coronary circulation with a specific
focus upon endothelin and oxidative stress in early coronary atherosclerosis
and endothelial dysfunction in humans; 2) to examine the associations
between conventional and non-conventional risk factors as well as genetic
predisposition and coronary endothelial function; 3) to develop novel non-invasive
tests as well as peripheral markers for early diagnosis of coronary
endothelial dysfunction; 4) to assess the relationship between coronary
endothelial function and structure in humans with early coronary
atherosclerosis; and 5) to address prospectively the prognosis of coronary
endothelial function in humans. The success of this program has the potential
to further both the research and mentoring endeavors of patient-oriented
investigation and mentoring the next generation of patient-oriented
Effective start/end date9/30/028/31/08


  • Medicine(all)